Urea cycle pathway targeted therapeutic action of naringin against ammonium chloride induced hyperammonemic rats

Arumugam, R.; Vijayakumar, Natesan

doi:10.1016/j.biopha.2017.08.028

Cited by 11 publications

(14 citation statements)

References 36 publications

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“…Under normal physiological conditions, blood NH 3 concentration is maintained at a low level, but damage to the liver or kidney can lead to elevated blood NH 3 [29]. Our results show that blood NH 3 levels were not different among the three groups, suggesting that CE had no negative effects on the health of the piglets, which is consistent with Ramakrishnan and Vijayakumar [28], who found that there were no significant differences between rats given naringin and control rats.…”

Section: Discussionsupporting

confidence: 90%

“…Both arginine and citrulline participate in the urea cycle [27], so these results imply that CE may affect the urea cycle. In support of this, it has been shown that citrus naringin can regulate proteins involved in the urea cycle pathway [28]. While this means that CE might be able to affect kidney function or citrulline uptake, there was no direct effect on urea in our study.…”

Section: Discussionsupporting

confidence: 68%

“…The feed consumption was measured every day to calculate the average daily feed intake (ADFI) and feed to gain ratio (F/G). Fresh fecal grab samples were collected in the morning during the last week (experimental d [21][22][23][24][25][26][27][28] and pooled by pen and stored at −20 • C for N and P emissions analysis. Each piglet was weighed at the end of the experiment, the two pigs closest to the average weight of treatments were selected from each replicate pen for slaughter.…”

Section: Sample Collection and Slaughter Proceduresmentioning

confidence: 99%

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Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Cui

Tian

Wang

et al. 2020

Animals

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The purpose of this study was to investigate the effects of citrus extract (CE) on plasma free amino acids, intestinal morphology and enzymes activity, fecal nitrogen and phosphorus emissions in piglets. The experiment was performed on 144 weaned piglets (Duroc × Landrace × Large White) divided into three groups. Control (CON), fed a basic diet; Antibiotic (ANTI), fed a basic diet supplemented with 75 g/t chlortetracycline; Citrus extract (CE), fed a basic diet supplemented with 300 mL/t CE. The albumin content of the CE group was significantly higher than the CON group. Compared with the CON and ANTI groups, the CE group had increased concentrations of plasma total essential amino acids and threonine. Compared with the CON group, CE increased the α-aminoadipic acid concentration, while compared with ANTI group, it increased the 3-methylhistidine concentration. Compared with the CON group, the crypt depth of duodenum, jejunum and ileum decreased, and the ratio of villus height to crypt depth of ileum increased in the ANTI and CE groups. CE increased the activity of alkaline phosphatase and lipase in duodenum, and the activity of alkaline phosphatase and trypsin in jejunum. In brief, CE improved the absorption and utilization of nitrogen, intestinal morphology and digestive enzymes activity.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 68%

Section: Sample Collection and Slaughter Proceduresmentioning

confidence: 99%

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Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Cui

Tian

Wang

et al. 2020

Animals

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“…Two flavonoids have been reported to decrease blood ammonia by increasing the expression of urea cycle enzymes [19][20][21][22][23] . However, whether this increased expression improves exercise endurance remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Flavonoids such as nobiletin 19 , naringin 20 , chrysin 21 , and fisetin 22,23 have been shown to improve ammonia resistance and up-regulate urea cycle enzymes 19,20,22 ; however, whether this up-regulation is effective for lowering exercise-induced hyperammonaemia remains unknown. One group of flavonoids, the green tea catechins (GTCs), have been shown to have several health-promoting impacts, including anti-cancer effects, hepatoprotective effects, anti-diabetic effects, and anti-obesity effects 24 ; however, the impact of GTCs on ammonia metabolism remains to be examined.…”

mentioning

confidence: 99%

Involvement of ammonia metabolism in the improvement of endurance performance by tea catechins in mice

Chen

Minegishi

Hasumura

et al. 2020

Sci Rep

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Blood ammonia increases during exercise, and it has been suggested that this increase is both a central and peripheral fatigue factor. Although green tea catechins (Gtcs) are known to improve exercise endurance by enhancing lipid metabolism in skeletal muscle, little is known about the relationship between ammonia metabolism and the endurance-improving effect of GTCs. Here, we examined how ammonia affects endurance capacity and how GTCs affect ammonia metabolism in vivo in mice and how GTCs affect mouse skeletal muscle and liver in vitro. in mice, blood ammonia concentration was significantly negatively correlated with exercise endurance capacity, and hyperammonaemia was found to decrease whole-body fat expenditure and fatty acid oxidation-related gene expression in skeletal muscle. Repeated ingestion of Gtcs combined with regular exercise training improved endurance capacity and the expression of urea cycle-related genes in liver. In C2C12 myotubes, hyperammonaemia suppressed mitochondrial respiration; however, pre-incubation with Gtcs rescued this suppression. together, our results demonstrate that hyperammonaemia decreases both mitochondrial respiration in myotubes and whole-body aerobic metabolism. thus, Gtc-mediated increases in ammonia metabolism in liver and resistance to ammonia-induced suppression of mitochondrial respiration in skeletal muscle may underlie the endurance-improving effect of GTCs.Exercise-induced fatigue is an important concern in sports, exercise, and rehabilitation because it is unavoidable and its early onset can hinder people from accomplishing their goals. Exercise-induced fatigue is commonly assessed as endurance capacity, based on the assumption that time to exhaustion correlates with the force generating capacity of muscle, and it is attributed to multiple factors, including the accumulation of fatigue metabolites, depletion of muscle glycogen, decrease of muscle pH, increase of muscle temperature, and production of inflammatory cytokines 1,2 . The complexity of the mechanisms underlying the development of exercise-induced fatigue makes it difficult to find approaches to mitigate its effects.Ammonia is a ubiquitous waste product of the metabolism of nitrogenous compounds, including amino acids and proteins, and has long been considered both a central and peripheral factor in the onset of exercise-induced fatigue 3 . During exercise, ammonia is produced via deamination of adenosine monophosphate 4,5 and the breakdown of branched-chain amino acids in skeletal muscle 6,7 . The production of ammonia increases with increasing intensity and duration of exercise [8][9][10] . Although the ammonia fatigue theory is not new, there remains a lack of conclusive evidence proving the roles of ammonia in the onset and development of exercise-induced fatigue.Recent evidence from exercise and disease studies has provided new insights into the role of ammonia during exercise. For example, it has been reported that ammonia activates phosphofructokinase and inhibits the oxidation of pyruvate to acety...

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Naringin corrects renal failure related to Lesch‐Nyhan disease in a rat model via NOS–cAMP–PKA and BDNF/TrkB pathways

Akintunde,

Falomo,

Akinbohun

et al. 2023

J Biochem & Molecular Tox

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This study explored the effect of naringin (NAR) on HGPRT1 deficiency and hyperuricemia through NOS–cAMP–PKA and BDNF/TrkB signaling pathways induced by caffeine (CAF) and KBrO3 in a rat model. Sixty‐three adult male albino rats were randomly assigned into nine (n = 7) groups. Group I: control animals, Group II was treated with 100 mg/kg KBrO3, Group III was treated with 250 mg/kg CAF, Group IV was treated with 100 mg/kg KBrO3 + 250 mg/kg CAF, Group V was administered with 100 mg/kg KBrO3 + 100 mg/kg haloperidol, Group VI was administered with 100 mg/kg KBrO3 + 50 mg/kg NAR, Group VII was administered with 500 mg/kg CAF + 50 mg/kg NAR, and Group VIII was administered with 100 mg/kg KBrO3 + 250 mg/kg CAF + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The exposure of rats to KBrO3 and CAF for 21 days induced renal dysfunction linked with Lesch‐Nyhan disease. NAR obliterated renal dysfunction linked with Lesch‐Nyhan disease by decreasing uric acid, renal malondialdehyde level, inhibiting the activities of arginase, and phosphodiesterase‐51 (PDE‐51) with corresponding upregulation of brain derived‐neurotrophic factor and its receptor (BDNF‐TrkB), Bcl11b, HGPRT1, and DARPP‐32. Additionally, renal failure related to Lesch‐Nyhan disease was remarkably corrected by NAR as shown by the reduced activities of AChE and enzymes of ATP hydrolysis (ATPase, AMPase, and ADA) with affiliated increase in the NO level. This study therefore validates NAR as nontoxic and effective chemotherapy against kidney‐related Lesch‐Nyhan disease by mitigating effects of toxic food additives and enzymes of ATP‐hydrolysis via NOS–cAMP–PKA and BDNF/TrkB signaling pathways.

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Urea cycle pathway targeted therapeutic action of naringin against ammonium chloride induced hyperammonemic rats

Cited by 11 publications

References 36 publications

Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Citrus Extract Improves the Absorption and Utilization of Nitrogen and Gut Health of Piglets

Involvement of ammonia metabolism in the improvement of endurance performance by tea catechins in mice

Naringin corrects renal failure related to Lesch‐Nyhan disease in a rat model via NOS–cAMP–PKA and BDNF/TrkB pathways

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